Download INSTRUCTION SHEET on Medical Application of the Preparation

INSTRUCTION SHEET
on Medical Application of the Preparation
RANITIDINE - AKOS
Registration number:
Preparation trade name: Ranitidine-AKOS
International nonproprietary name: Ranitidine
Dosage form: film coated tablets.
Composition:
Active substance: ranitidine hydrochloride (on ranititidine basis) - 150 mg, 300 mg;
Excipents: corn starch, lactose monohydrate (milk sugar), microcrystalline cellulose, low-molecular
povidone (medicinal low-molecular polyvinylpyrrolidone 12600 ± 2700), calcium stearate,
crospovidone (kollidon CL).
Film coating: hypromellose (oxypropylmethylcellulose), macrogol-4000 (polyethyleneglycol
4000), tropeolinum 0, titanium dioxide, propylene glycol, talcum powder.
Description:
Yellow round biconvex film-coated tablets
Pharmacotherapeutic group: The preparation decreases the secretion of gastric glands, histamine
Н2-receptor antagonist
ATC code: [A02BA02]
Pharmacological effect:
Ranitidine is an antagonist of histamine Н2- receptors of the second generation. The mechanism of
action is connected with the blockade of histamine Н2-receptors of membranes of gastric mucosa
parietal cells. It inhibits day and night secretion of HCl as well as basal and stimulated secretion,
decreases the volume of gastric juice caused by gastric distention due to food load, action of
hormones and biogenic stimulants (gastrin, histamine, acetylcholine, pentagastrin, caffeine).
Ranitidine reduces the amount of HCl in the gastric juice almost not inhibiting hepatic enzymes
connected with the P450 cytochrome, does not affect the gastrin concentration in plasma and mucus
production. It decreases the pepsin activity.
Ranitidine does not affect the Ca2+ concentration in blood serum. After oral administration in
therapeutic doses the preparation does not affect the prolactin concentration (after intravenous
administration of ranitidine at a dose of 100mg and more, insignificant and transient increase of
prolactin concentration in blood serum is possible).
Ranitidine does not affect the releasing of hypophysis hormones: gonadotropin, thyrotropic
hormone and somatotropic hormone. It does not affect the concentration of cortisol, aldosterone,
androgens or estrogens as well as spermatozoon motility, sperm amount and sperm structure. It
does not produce the antiandrogenic action.
It may reduce vasopressin releasing.
Ranitidine increases defence mechanisms of gastric mucosa and heals its damage associated with
the HCl action (it helps to terminate gastrointestinal hemorrhage and to heal stress ulcers) through
the increase of production of gastric mucin and its glycoproteins, stimulation of secretion of
hydrocarbonate by gastric mucosa, endogenous Pg synthesis in gastric mucosa and regeneration
speed. At a dose of 150mg ranitidine inhibits secretion of gastric juice for 8 to 12 hours. It inhibits
microsomal enzymes (less than cimetidine).
Pharmacokinetics. Ranitidine is quickly absorbed; food intake does not affect the absorption rate.
The ranitidine bioavailability is 50%. The maximum concentrations is 150mg of ranitidine. The
time of attaining of maximum concentration is 2-3 hours. Connection with plasma proteins is
15%. It poorly penetrates through hematoencephalic barrier. It penetrates through placental barrier
and into breast milk (concentration in women’s milk during lactation period is higher than in
plasma). Ranitidine is little metabolized in liver with formation of desmethylranitidine and
1
ranitidine S-oxide. It has a first pass effect. The elimination rate and level very little depend on
the liver condition. The half-life period (if creatinine clearance is normal) is 2.5 hours. If the
creatinine clearance is 20-30 ml/min, the half-life period is 8-9 hours.
Ranitidine is excreted by kidneys – 69-70% (mainly in unchanged form – 35%) and intestine.
Indications for application:
Treatment and prevention: gastric ulcer and duodenal ulcer, NSAID-gastropathy, epigastric
burning (associated with hyperacidity), hypersecretion of gastric juice, symptomatic ulcers, stress
ulcers of the gastrointestinal tract, erosive esophagitis, reflux esophagitis, Zollinger-Ellison
syndrome, systemic mastocytosis, multiple endocrine adenomatosis, dyspepsia characterized by
epigastric or retrosternal pains associated with intake of food or disturbing sleep but not caused by
the above conditions, treatment of bleeding from upper gastrointestinal tract, prevention of
recurrence of gastric bleeding in the postoperative period, prevention of aspiration of gastric juice in
patients undergoing surgery under general anesthesia (Mendelson's syndrome), aspiration
pneumonitis (prevention), rheumatoid arthritis (as an adjuvant therapy).
Counterindications:
Hypersensitivity, lactation period.
With caution
Renal and/or hepatic insufficiency, liver cirrhosis with encephalopathy in the past medical history,
acute porphyria (including in past medical history), immunosuppression, children’s age (under 12
years), pregnancy.
Category of effects on the fetus: B (studies of reproduction in animals showed no risk of adverse
action to the fetus, but no adequate and well-controlled clinical studies in pregnant women have
been conducted).
Method of application and dosage:
Oral administration: gastric ulcer and duodenal ulcer (in the acute condition), postoperative ulcers
– 150mg twice a day or 300mg for the night for 4-8 weeks. In patients with not healed ulcers during
this period: continuation of the treatment for the subsequent 4 weeks.
Prevention of recurrence: 150mg for the night; for smoking patients – 300mg for the night.
NSAID-gastropathy: 150mg twice a day or 300mg for the night for 8-12 weeks; prevention –
150mg twice a day.
Erosive reflux – esophagitis: 150mg twice a day or 300mg for the night for 8 weeks; if necessary,
the course of treatment may be continued up to 12 weeks. Long-term preventional therapy: 150mg
twice a day.
Zollinger-Ellison syndrome: the initial dose is 150mg 3 times a day; the dose may be increased to
6g/day if necessary.
Chronic episodes of dyspepsia: 150mg twice a day for 6 weeks.
Treatment of peptic ulcer in children: 2-4 mg/kg twice a day; reflux – esophagitis – 2-8 mg/kg 3
times a day; maximal daily dose is 300mg.
Patients with impaired kidney function require correction of the dosage regimen. If the creatinine
clearance is less than 50 ml/min, the recommended dose is 150mg/ day. In patients with
concomitant compromised liver function, additional reduction of the dose is recommended.
Patients with hemodialysis: the next dose is administered right after hemodialysis termination.
Side effects:
Digestive system: nausea, dryness in the mouth, constipation, vomiting, diarrhea, abdominal pains,
jaundice, increase of activity of hepatic transamenases; rarely - hepatocellular, cholestatic or
combined hepatitis, acute pancreatitis.
Blood-forming organs:
leukopenia,
thrombocytopenia, agranulocytosis, pancytopenia,
neutropenia, immune hemolytic or aplastic anemia.
2
Cardiovascular system: lowering of blood pressure, bradycardia, tachycardia, vasculitis, arrythmia,
atrioventricular blockade.
Nervous system: headache, dizziness, hyperthermia, increased fatigability, sleepiness, sleep loss,
emotional lability, anxiety, psychic tension, depression, nervousness; rarely - confused mental
state, buzzing in ears, fretful temper, hallucinations (mainly in elderly patients and bad cases),
notwilled movements.
Sense organs: bad visual perception, paresis of accommodation.
Locomotor system: arthralgia, myalgia.
Endocrine system:
hyperprolactinemia,
gynecomastia, amenorrhea, libido and/or potency
lowering.
Allergic reactions: generalized rash, skin eruption, itching, angioneurotic edema, anaphylactic
shock, bronchismus, multiform exudative erythema, including Stevens-Johnson syndrome,
exfoliative dermatitis, toxic epidermal necrolysis.
Other: alopecia.
Overdosage
Symptoms: convulsions, bradycardia, ventricular arrhythmia.
Treatment: symptomatic. In case of oral administration, induction of vomiting or/and gastric
lavage are recommended. If convulsions occur, diazepam should be intravenously administered,
in patients with bradycardia - atropine, in patients with ventricular arrhythmia - lidocaine.
Hemodialysis is effective.
Interaction with other medicinal preparations
Ranitidine increases the area under the concentration-time curve (AUC) and concentration of
metoprolol in blood serum (by 80% and 50% respectively). In addition, the half-life of metoprolol
increases from 4.4 to 6.5 hours.
Ranitidine decreases absorption of itraconasole and ketoconazole. It inhibits metabolism of
phenazone,
aminophenazone,
diazepam, hexobarbital, propranolol, metoprolol, nifedipine,
warfarin, diazepam, lidocaine, phenytoin, theophyllin, aminophylline, indirect anticoagulants,
glipizide, buformin, metronidazole, calcium channel-blocking agents in liver. It increases the
procainamide concentration.
Antacids, sucralfate slow down the ranitidine absorption (during simultaneous administration the
interval between administrations of antacids and ranitidine should be at least 1-2 hours)
Drugs inhibiting the bone marrow increase the risk of neutropenia.
Smoking reduces the efficacy of ranitidine.
Special instructions
Symptoms of duodenal ulcer may disappear for 1-2 weeks; the therapy should be continued until
the healing is confirmed by the results of endoscopic or X-ray examination.
Ranitidine treatment can conceal symptoms associated with stomach carcinoma, thus, before
treatment it is necessary to exclude the presence of cancer.
It is not recommended to suddenly terminate ranitidine (ricochet syndrome).
In case of long-term treatment of debilitated patients under stress, bacterial stomach disorders
followed by infection expansion are possible.
Blockers of Н2-histamine receptors should be administered in 2 hours after administration of
itraconasole or ketoconazole in order to avoid significant reduction of their absorption.
It may be a reason of false-positive reaction during the test for protein in the urine.
Ranitidine increases the level of creatinine, gamma-glutamyl transferase and transaminases in blood
serum.
Ranitidine counteracts the effect of pentagastrin and histamine on acid-forming stomach function,
therefore, it is not recommended to administer it within 24 hours prior to the test.
The histamine skin reaction is inhibited leading in this way to false-negative results (before
diagnostic skin tests for revelation of allergic immediate-type skin reaction, administration of the
3
drug should be terminated).
The efficacy of the drug relating to inhibition of night secretion of acid in stomach may be reduced
in smoking patients.
During treatment it is necessary to avoid foodstuffs, drinks and other medicinal agents which may
cause stomach mucous membrane irritation.
If no improvement is noticed, the doctor’s consultation is required.
During treatment caution should be exercised when driving a car or conducting other potentially
dangerous types of activity requiring enhanced attention concentration and quickness of psychomotor
reactions.
Form of product
150mg and 300mg film coated tablets.
10 tablets per blister cellular pack. 1 or 2 blister cellular packs with an instruction leaflet per
cardboard pack.
Period of validity
3 years. Do not use after expiration of the date specified on the pack.
Storage conditions
List B. Store in a dry dark place at a temperature of not more than 25°С. Keep out of reach of
children.
Conditions of supply from chemist’s shops
On doctor’s prescription.
Manufacturer/organization that accepts claims:
Open Joint Stock “Kurgan Joint Stock Company of Medical Preparations and Articles “Sintez”
(Sintez Joint Stock Company);
#7, Prospect Konstitutsii, city of Kurgan, Russian Federation, 640008;
Tel. /fax: (3522)481689
Internet-site: http://www.kurgansintez.ru
4